Mitosis and Meiosis/ Nondisjunction

Mitosis

Mitosis Divides Somatic Cells

  • Mitosis is a genetically controlled process essential for growth, development, and maintenance of organisms

    • A replicated chromosome donates one of its two identical twin sister chromatids to each daughter cell

  • Proper regulation is crucial as insufficient cell division can result in development failure or abnormalities (nondisjunction)

Quantifying Chromosomes

  • A chromosome is a molecule of condensed DNA and associated proteins

    • Can be unreplicated (monad) or replicated (dyad/bound by a centrosome)

  • Ploidy represents the number of chromosome sets by (n)

    • Pick a chromosome, how many match it?

      • 1n = haploid ; 1 complete set of non-homologous chromosomes 

      • 2n = diploid ; 2 complete sets of non-homologous chromosomes 

        • Homologous chromosomes = same sizes and genes in same locations

    • During mitosis, ploidy is maintained from beginning to the end because we want identical daughter cells

      • Starts as 2n going into mitosis, by metaphase the chromatids are separated and by anaphase it s 4n, and finishes as 2n as it combines with other chromosomes

  • Human Karyotype is categorized by first 22 being autosomes (longest to shortest) and the last pair being sex chromosomes 

  • Amount of mass in DNA is represented by ©

    • c= one set of all the genes in the genome; how many homologous chromatids?

      • 1c = mass of one full set of non-homologous chromosomes

      • 2c = 2 complements of the genome

        • Either as sister chromatids or as homologous monad chromosomes

      • 4c = 4 complements of the genome

        • 2 on sister chromatids and 2 homologous chromosomes

    • How much DNA there is and it can change with ploidy and by changing replication

    • Begins as 4c as there is a total of 4 chromosomes after replication

      • Becomes 2c after combination of new chromosomes

    • If a cell in G1 is diploid (2 sets of unreplicated chromosomes), it is 2c 

      • S doubles DNA mass while maintaining chromosome count

The Cell Cycle

  • Cell division is regulated by the cell cycle, essential for DNA replication and cell division

  • There are two main phases:

    • Interphase: Normal cellular function and preparation for cell division

      • G1, S, and G2 (longer stage)

    • Mitosis: Division into identical daughter cells

Interphase

  • G1: active gene expression and cell activity for DNA synthesis

    • At the end, cells can either enter the S phase for DNA replication or transition to a non dividing stage called G0

      • G0: express genetic information but do not divide 

    • Grows in size, getting larger and gets checked by a checkpoint to see if cell size is adequate, and if growth factors are present to regulate cell division

      • Most susceptible to external environments here

  • S: results in two identical sister chromatids for each chromosome, doubling the DNA amount in the nucleus

    • Must go through checkpoint, only if replication is complete and has been screened to remove base-pair mismatch (no mismatch detected)

      • Won’t move to G2 if mismatch is detected

  • G2: cells prepare for division with more growth and contains DNA that is fully synthesized

    • If the cell enters mitosis without synthesis of DNA, it could lead to unequal distribution genes, which won’t provide identical daughter cells at the end of mitosis

    • Passes checkpoint to make sure the above scenario occurs and there are no unmatched DNA

  • Interphase ends as cells enter M phase and successful cell generations produced through mitosis are called cell lines (genetically identical cells)

Mitosis

  • During interphase, DNA is condensed, and chromosomes are not visible under light

    • Chromosome condensation occurs in early prophase; nuclear envelope breakdown occurs in prophase, revealing chromosome centromeres 

      • Centromeres are specialized DNA sequences where sister chromatids are joined; binds the kinetochore protein complex for chromosome movement and division

  • By the end of prometaphase, kinetochore microtubules from each centrosome attach to kinetochore protein on chromatids (each chromatid)

  • During metaphase, chromosomes condense making them visible; positions chromosomes along the metaphase plate due to opposing forces from microtubules

    • Uses cohesion to balance sister chromatids, produced by cohesin

      • Cohesin localizes between sister chromatids and joins/holds them together

      • Ensures proper chromosome positioning and prevents premature separation

    • Separase is an enzyme that degrades cohesin to initiate anaphase and separate sister chromatids

      • You do not want separase all the time though because if so, cohesin will always be degraded and chromatids will be degraded before being separated into two cells

      • Spindle checkpoint before anaphase however, makes sure that chromosomes are lined up and will trigger the release of enzymes (separase) to initiate the separation of chromatids and degradation of cohesin

  • Anaphase involves the separation of sister chromatids with separase and the elongation of the cell into an oblong shape due to the polymerization of polar microtubules

  • During telophase, nuclear membranes reassembles around chromosomes at each pole, forming the nuclear envelope

    • Chromosomes decondense and microtubules disassemble

    • By the end, two identical nuclei are present in a single elongated cell divided by cytokinesis 

  • Cytokinesis divides the cytoplasmic fluid and organelles 

    • At the end of mitosis, there are 46 chromosomes ready to enter the next cell cycle of G1 again

Microtubules and Structure

  • Centrosomes migrate to form the two opposite poles of the dividing cell during Mitosis

    • Each centrosome contains a pair of centrioles as a source of spindle fiber microtubules 

    • These spindle fiber microtubules are polymers of tubulin protein 

    • These microtubules are polar with a (-) charge end at the centrosome, and a (+) end that grows away from the centrosome 

    • Motor proteins are specialized proteins with microtubules that move chromosomes and other cell structures along the microtubules

      • Enzymes and create energy to move things and carry anything

  • Microtubules divide the chromosomes

    • Three types of spindle fibers (microtubules) that come from centrosomes:

      • Kinetochore microtubules: embed in the kinetochore at the centromere of each chromatid and are responsible for chromosome movement

        • Kinetochore is a protein complex at the centromere of each chromatid that attaches to the plus end of a kinetochore microtubule

      • Polar microtubules: extend toward the opposite pole of the centrosome and contribute to cell elongation and cell stability 

        • Links to motor proteins

      • Astral microtubules: grow toward the membrane of the cell and contribute to cell stability

        • Distribute pressure across pole surface to pull cell apart

Meiosis

Meiosis Produces Cells for Sexual Reproduction

  • Meiosis is the creation of gametes that are genetically different for sexual reproduction, increasing genetic diversity 

    • Different reactions to different environmental impacts 

    • The result is the fusion of 2 gametes

      • One gamete fuses with another, mixes and combines to increase genetic diversity and maintaining ploidy throughout generations

    • To maintain species ploidy, gametes must have ½ the chromosomes

  • Meiosis involves two successive cell divisions during its’ phase, distinct movements of homologous chromosomes and sister chromatids, ultimately resulting in 4 haploid gametes

  • Prophase is separated into 5 divisions:

    • Leptotene: thin/fine threads where chromosomes begin to condense

    • Zygotene: joined/yoked threads where homologous chromosomes synapse (not identical, but from each parent)

      • This synapsis leads to the formation of the synaptonemal complex: tightly binds non sister chromatids of homologous chromosomes

        • Properly aligns homologous chromosomes

        • Allows for recombination

      • Homologous chromosome synapsis is dependent on DNA sequence similarity/homology. But in males, X and Y are very different. How do these pair?

        • There are special caps/small regions that are similar enough to pair at tips

        • Micro Analogies can be enough to pair and match

          • PAR = pseudoautosomal region allows for temporary pairing as these PARs are located at the ends of chromosomes

    • Pachytene: thick threads where crossing over occurs

      • Homologous chromosomes exchange some parts of sequence with another homologous chromosome 

      • Kinetochore microtubules also connect to kinetochore

      • Recombination nodules appear within the central element of the synaptonemal complex and are crucial for crossing over between nonsister chromatids

    • Diplotene: double threads where synaptonemal complex degrades and holds proteins together; reveals chiasmata

      • Chiasmata: indicate locations of DNA-strand exchange between nonsister chromatids; crossing over location

      • Cohesin proteins maintains the connection between sister chromatids against the pulling forces of kinetochore microtubules

    • Diakinesis: moving across where homologous pairs approach metaphase and prepare to move towards the middle

      • Due to the resolution of chiasmata, homologous chromosomes can line up in the middle

  • Metaphase I consists of homologous chromosomes aligning on opposite sides of the metaphase plate

    • Tetrads align on metaphase plate (chromosome pairs)

    • Chiasmata breaks

    • Sister chromatids remain attached via cohesion at the centromere

    • Kinetochore microtubules attach to both sister chromatids of one homologous chromosome; kinetochore microtubules from the opposite pole do the same for the other homologous chromosome

    • Responsible for the Law of Independent Assortment:

      • The inheritance of an allele of one gene does not depend on the inheritance of an allele of a second gene

      • Each chromosome is independent to move into any other arrangement, therefore, there are arrangements that are equally likely

        • “G” is equally likely to be inherited with “R” as it is with “r”

  • Anaphase I: kinetochore microtubules depolymerize; moves homologous chromosomes to opposite poles

    • Cohesin between sister chromatids is maintained

  • Telophase I: new nuclear envelope forms haploid nuclei (2)

    • Meiosis I is reduction division, meaning reduced ploidy (2n → n) because of separation of homologous chromosomes

Meiosis II

  • Similar to mitosis in which it is the separation of sister chromatids to create 4 genetically different haploid cells

    • PMAT II

    • Breakdown of cohesin, motor proteins, and microtubule depolymerization

  • Anaphase II reduces DNA, chromosomes, and chromatids by half, resulting in gametes with 23 chromosomes

Sex Determination

  • Number of copies can matter at some times such as in honeybees, or environment can matter such as in crocodilians, however, most of the time the X and Y determine the sex of the organism

    • In birds, it is Z where ZZ is male and ZW is female (opposite from humans of XX female and XY male)

    • Grasshoppers either have one X for male (XO) or XX for female

  • SRY is the gene for male-specfic transcription factors on Y chromosome

    • Early mammalian embryos have clusters of tissue called undifferentiated gonads, which can develop as ovaries or testes

    • The expression of SRY initiates testicular development of the undifferentiated gonads

    • The absence of SRY expression allows the default state, female, to develop

    • In XXY?

      • If there are too many autosomes, individuals won’t develop properly (like 13, 21), but if it occurs in sex chromosomes such as XXY, it can develop properly

      • If there is no Y in the sex chromosomes, it is fine to develop (or even if Y is there), but if there is no X, it can be lethal

      • Assuming SRY is expressed, a male would develop in XXY

Mitosis v Meiosis


Mitosis

Meiosis

Genetically identical cells for growth and maintenance

Genetically different gametes for sexual reproduction

Somatic cells

Germ-line cells

One round of division following one round of DNA replication

Two rounds of division following one round of DNA replication

Homologous chromosomes do not pair and rarely undergo recombination

Homologous chromosomes undergo synapsis and crossing over

Two genetically identical diploid daughter cells

Four genetically different haploid cells maturing into gametes


Nondisjunction

10.2: Nondisjunction Leads to Changes in Chromosome Number

  • Nondisjunction is the failure of chromosomes and sister chromatids to properly separate during cell division, ultimately causing abnormalities of chromosome number in cells

    • Changes in chromosome number exert effects by addition or removal of one or more chromosomes of the normal complement nucleus 

    • These abnormalities almost always alter the phenotype and can have an effect on the development/reduce fertility and viability of the organism

    • Can happen in meiosis I or meiosis II

Chromosome Nondisjunction

  • The number of chromosomes is usually the SAME for males and females of a species

    • The number of chromosomes in nuclei of normal cells is a multiple of the haploid number (n), the number in a single set of chromosomes

  • Chromosome numbers that are a multiple of the haploid number (3n, 4n, etc.) are euploid

    • The addition or removal of a chromosome alters the euploid number and generates a chromosome count known as aneuploidy 

      • Chromosome nondisjunction is the cause of aneuploidy 

      • Aneuploidy also means incomplete sets of chromosomes

  • Meiotic nondisjunction can occur in either Meiosis I or II and affect just a single homologous pair/single pair of sister chromatids in a gametocyte

    • Meiotic I nondisjunction: failure of homologous chromosomes to separate, resulting in both homologous chromosomes moving to a single pole and contains both chromosomes in a singular gametocyte, while the other gametocyte contains no chromosomes

      • These gametocytes contain aneuploid chromosome numbers of n + 1 and n - 1 and after the fertilization with a normal gamete, a fertilized egg with an aneuploid number of chromosomes either trisomic (2n + 1), having three of one of the chromosomes rather than a pair, or monosomic (2n - 1), having a single copy of one of the chromosomes rather than a pair

        • In trisomic the 2n comes from the two chromosomes in the aneuploid gamete, that then fuse with a normal gamete with one chromosome, where the 1 comes from

        • In monosomic the 2n is what should be there, however, because there were no chromosomes in the aneuploid gamete, that then fused with a normal gamete of one chromosome, there is only one chromosome in the fertilized egg resulting in 2n - 1

    • Meiotic II nondisjunction: proceeds normally and its completion sends the sister chromatids to different gametes.

      • Follows the first meiosis, meaning that if nondisjunction occurs, it is within only one of the secondary gametes

      • Makes two become normal because of a normal disjunction, and leaves two gametes to become aneuploid with one containing n + 1 and n - 1 chromosomes 

        • Also produces aneuploid gametes that unite with normal gamete at fertilization 

  • Sometimes, nondisjunction can occur within sex chromosomes

    • Individuals often reach maturity but often infertile, however, we won’t know much about this issue until these women have children

    • Only trisomies of chromosomes 13, 18, and 21 are observed in newborns → an addition of 22 can then make the statement true that there can be severe defects within these newborns that result in less chances to survive in adulthood

      • XXY → Klinefelter syndrome

      • XYY → Jacob syndrome

      • XXX → Triple X syndrome

      • XO → Turner syndrome 

      • OY → non viable zygotes as it lacks an X Chromosome → therefore, wouldn’t develop

10.3: Changes in Euploid Content Lead to Polyploidy

  • Polyploidy is the presence of three or more sets of chromosomes in the nucleus of an organism

    • Common in plants and can arise from either a duplication of entire chromosome sets or combination of chromosome sets from different species

      • When ALL chromosomes improperly segregate

      • Colchicine prevents separation of sister chromatids and can induce polyploidy as it disrupts anaphase

    • Autopolyploids have chromosomes derived from a single species

    • Allopolyploids have chromosomes sets from two or more species 

  • When produced for commercial purposes, plant polyploidy has three main consequences:

    • 1. Fruit and flower size are increased as the cells grow larger 

      • Bread wheat (6n), Durum wheat (4n), Bananas (3n), Strawberries (8n) seem to have very little problem with this as it does not affect a cell’s ability to undergo mitosis

        • It can grow and develop fine, but polyploidy can interfere with meiosis

    • 2. Cost of fertility

      • Odd numbered polyploids cannot be evenly divided at the first meiotic division, resulting in an unequal distribution of chromosomes making all gametes non viable

        • This can be an advantage at times where these fruits can make seedless versions of themselves due to the unequal distribution and stopping of growth 

      • These seeds also don’t have a problem with viability (able to work successfully) because they still grow regardless in the mitosis phase, therefore, sister chromatids get separated into 2 cells and grow

        • Because homologous chromosome pairing only occurs in meiosis, they do not have to worry about doing so as they can still grow with only mitosis

      • Meiosis in triploids results in true and independent chromosomes where random assortment of aneuploidy occurs within gametes

        • If you repeat this, every gamete will have a random mix of 1 (correct) or 2 (one extra) homologous chromosomes, making it hard for seeds to develop normally 

        • This random mix makes it hard for the seeds to get the correct amount of chromosomes to develop

    • 3. Increase in heterozygosity relative to diploids that comes about when inbred lines are crossed

  • Causes/mechanisms of autopolyploidy

    • 1. Meiotic nondisjunction leading to a diploid rather than a haploid gamete 

      • Example: 2n (egg) +  n (pollen) → 3n plant

      • Or 2n (egg) + 2n (pollen) → 4n 

    • 2. Mitotic nondisjunction that doubles chromosome number

      • Example: 2n cell ND → 4n cell (doubled)

      • Can also combine where there is a 2n egg + n pollen → 3n and doubles → 6n to increase polyploidy

  • Causes of allopolyploidy

    • Hybrids with chromosomes from different species

    • Infertile due to nonhomologous chromosomes that cannot pair in meiosis

    • The union of a haploid gamete from species 1 (n1) and a haploid gamete from species 2 (n2) produces a hybrid organisms that can either have a even or odd number of chromosomes depending on the haploid number that is normal for each species

      • As these chromosomes are nonhomologous, they have difficulty pairing, however, with the help of mitotic duplication of chromosomes, the total chromosome number can double and generate pairs of chromosomes by nondisjunction

      • Now the homologous chromosomes each have a pair for one another and the hybrid is fertile

Past Terminology

  • 1n = haploid → meaning there is 1 complete set of non-homologous chromosomes

  • 2n = diploid → 2 complete sets of chromosomes